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The importance of protein glycosylation in the migration of immune cells throughout the body has been extensively appreciated. However, our awareness of the impact of glycosylation on the regulation of innate and adaptive immune responses is relatively new. An increasing number of studies reveal the relevance of glycosylation to pathogen recognition, to the modulation of the innate immune system and to the control of immune cell homeostasis and inflammation. Similarly important is the effect of glycan-containing 'information' in the development of autoimmune diseases and cancer. In this review, we provide an overview of these new directions and their impact in the field of glycoimmunology.

Tumours are occasionally transferred from donor to recipients during organ transplantation. This paper shows in a mouse model that during latency tumours are actively held in check by the adaptive immune system. The capacity of immunity to control and shape cancer, that is, cancer immunoediting, is the result of three processes 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 that function either independently or in sequence 9 : elimination (cancer immunosurveillance, in which immunity functions as an extrinsic tumour suppressor in naive hosts); equilibrium (expansion of transformed cells is held in check by immunity); and escape (tumour cell variants with dampened immunogenicity or the capacity to attenuate immune responses grow into clinically apparent cancers). Extensive experimental support now exists for the elimination and escape processes because immunodeficient mice develop more carcinogen-induced and spontaneous cancers than wild-type mice, and tumour cells from immunodeficient mice are more immunogenic than those from immunocompetent mice. In contrast, the equilibrium process was inferred largely from clinical observations, including reports of transplantation of undetected (occult) cancer from organ donor into immunosuppressed recipients 10 . Herein we use a mouse model of primary chemical carcinogenesis and demonstrate that equilibrium occurs, is mechanistically distinguishable from elimination and escape, and that neoplastic cells in equilibrium are transformed but proliferate poorly in vivo . We also show that tumour cells in equilibrium are unedited but become edited when they spontaneously escape immune control and grow into clinically apparent tumours. These results reveal that, in addition to destroying tumour cells and sculpting tumour immunogenicity, the immune system of a naive mouse can also restrain cancer growth for extended time periods.

Maternal inflammation and diabetes increase the risk for psychiatric disorders in offspring. We hypothesized that these co-occurring risk factors may potentiate each other. To test this, we maternally exposed developing mice in utero to gestational diabetes mellitus (GDM) and/or maternal immune activation (MIA). Fetal mouse brains were exposed to either vehicle, GDM, MIA or GDM+MIA. At gestational day (GD) 12.5, GDM produced a hyperglycemic, hyperleptinemic maternal state, whereas MIA produced significant increases in proinflammatory cytokines and chemokines. Each condition alone resulted in an altered, inflammatory and neurodevelopmental transcriptome profile. In addition, GDM+MIA heightened the maternal inflammatory state and gave rise to a new, specific transcriptional response. This exacerbated response was associated with pathways implicated in psychiatric disorders, including dopamine neuron differentiation and innate immune response. Based on these data, we hypothesize that children born to GDM mothers and exposed to midgestation infections have an increased vulnerability to psychiatric disorder later in life, and this should be tested in follow-up epidemiological studies.

The innate immune cell network detects specific microbes and damages to cell integrity in order to coordinate and polarize the immune response against invading pathogens. In recent years, a cross‐talk between microbial‐sensing pathways and endoplasmic reticulum (ER) homeostasis has been discovered and have attracted the attention of many researchers from the inflammation field. Abnormal accumulation of proteins in the ER can be seen as a sign of cellular malfunction and triggers a collection of conserved emergency rescue pathways. These signalling cascades, which increase ER homeostasis and favour cell survival, are collectively known as the unfolded protein response (UPR). The induction or activation by microbial stimuli of several molecules linked to the ER stress response pathway have led to the conclusion that microbe sensing by immunocytes is generally associated with an UPR, which serves as a signal amplification cascade favouring inflammatory cytokines production. Induction of the UPR alone was shown to promote inflammation in different cellular and pathological models. Here we discuss how the innate immune and ER‐signalling pathways intersect. Moreover, we propose that the induction of UPR‐related molecules by microbial products does not necessarily reflect ER stress, but instead is an integral part of a specific transcription programme controlled by innate immunity receptors. Philippe Pierre and colleagues discuss the emerging links between the ER stress and innate immune response pathways, and how they intersect to regulate inflammation.

In all animal models for chlamydial infection, there is strong evidence for immunity to reinfection; however, immunity is only complete (ie, preventing infection) in the short term. In the long term, animals are only partially immune (ie, they can be reinfected, but infections are usually abbreviated and less intense than the primary infection). This review will target the mechanisms responsible for long-term versus short-term immunity and explore the roles of various components of the host response in immunity to chlamydial genital infection.

It is becoming increasingly apparent that the causes of autism spectrum disorders (ASD) are due to both genetic and environmental factors. Animal studies provide important translational models for elucidating specific genetic or environmental factors that contribute to ASD-related behavioral deficits. For example, mouse research has demonstrated a link between maternal immune activation and the expression of ASD-like behaviors. Although these studies have provided insights into the potential causes of ASD, they are limited in their ability to model the important interactions between genetic variability and environmental insults. This is of particular concern given the broad spectrum of severity observed in the human population, suggesting that subpopulations may be more susceptible to the adverse effects of particular environmental insults. It is hypothesized that the severity of effects of maternal immune activation on ASD-like phenotypes is influenced by the genetic background in mice. To test this, pregnant dams of two inbred strains (that is, C57BL/6J and BTBR T + tf/J) were exposed to the viral mimic polyinosinic-polycytidylic acid (polyI:C), and their offspring were tested for the presence and severity of ASD-like behaviors. To identify differences in immune system regulation, spleens were processed and measured for alterations in induced cytokine responses. Strain-treatment interactions were observed in social approach, ultrasonic vocalization, repetitive grooming and marble burying behaviors. Interestingly, persistent dysregulation of adaptive immune system function was only observed in BTBR mice. Data suggest that behavioral and immunological effects of maternal immune activation are strain-dependent in mice.

The conventional classification of known immune responses by specificity may need re-evaluation. The immune system can be classified into two subsystems: the innate and adaptive immune systems. In general, innate immunity is considered a nonspecific response, whereas the adaptive immune system is thought of as being very specific. In addition, the antigen receptors of the adaptive immune response are commonly viewed as 'master sensors' whose engagement dictates lymphocyte function. Here we propose that these ideas do not genuinely reflect the organization of immune responses and that they bias our view of immunity as well as our teaching of immunology. Indeed, the level of specificity and mode of signaling integration used by the main cellular participants in the adaptive and innate immune systems are more similar than previously appreciated.

Uracil in DNA may result from incorporation of dUMP during replication and from spontaneous or enzymatic deamination of cytosine, resulting in U:A pairs or U:G mismatches, respectively. Uracil generated by activation-induced cytosine deaminase (AID) in B cells is a normal intermediate in adaptive immunity. Five mammalian uracil-DNA glycosylases have been identified; these are mitochondrial UNG1 and nuclear UNG2, both encoded by the UNG gene, and the nuclear proteins SMUG1, TDG and MBD4. Nuclear UNG2 is apparently the sole contributor to the post-replicative repair of U:A lesions and to the removal of uracil from U:G contexts in immunoglobulin genes as part of somatic hypermutation and class-switch recombination processes in adaptive immunity. All uracil-DNA glycosylases apparently contribute to U:G repair in other cells, but they are likely to have different relative significance in proliferating and non-proliferating cells, and in different phases of the cell cycle. There are also some indications that there may be species differences in the function of the uracil-DNA glycosylases.

Approximately 40–50% of individuals affected by tuberous sclerosis (TSC) develop autism spectrum disorders (ASDs). One possible explanation for this partial penetrance is an interaction between TSC gene mutations and other risk factors such as gestational immune activation. In this study, we report the interactive effects of these two ASD risk factors in a mouse model of TSC. Combined, but not single, exposure had adverse effects on intrauterine survival. Additionally, provisional results suggest that these factors synergize to disrupt social approach behavior in adult mice. Moreover, studies in human populations are consistent with an interaction between high seasonal flu activity in late gestation and TSC mutations in ASD. Taken together, our studies raise the possibility of a gene × environment interaction between heterozygous TSC gene mutations and gestational immune activation in the pathogenesis of TSC-related ASD.

In general, malaria immunity has been suggested to be species specific with very little, if any, known cross-reactivity between Plasmodium vivax and P. falciparum, both of which are responsible for >90% of human malaria, and co-endemic in many countries. It is therefore believed that species-specific immunity may be needed to target different species of Plasmodium. Pfs48/45 and Pvs48/45 are well established targets in the sexual stages of the malaria parasites, and are being pursued for the development of transmission blocking vaccines. Comparison of their sequences reveals 61% and 55% identity at the DNA and protein level, respectively raising the possibility that these two target antigens might share cross-reacting epitopes. Having succeeded in expressing recombinant Pfs48/45 and Pvs48/45 proteins, we hypothesized that these proteins will not only exhibit immunological cross-reactivity but also cross-boost immune responses. Mice were immunized with purified recombinant proteins using CFA, Montanide ISA-51 and alum as adjuvants, and the sera were analyzed by ELISA, Western blotting and indirect fixed and live IFA to address the hypothesis. Our studies revealed that Pvs48/45-immune sera showed strong cross-reactivity to full length Pfs48/45 protein, and the majority of this cross reactivity was in the amino-terminal and carboxyl-terminal sub-fragments of Pfs48/45. In cross-boosting experiments Pfs48/45 and Pvs48/45 antigens were able to cross-boost each other in mouse immunization studies. Additionally we also noticed an effect of adjuvants in the overall magnitude of observed cross-reactivity. These studies may have significant implications for immunity targeting transmission of both the species of malaria parasites.